Cariplo Giovani Corradini 2019-1973 - INTERPLAY BETWEEN IMMUNE MOLECULES AND THE EPIGENETIC FACTOR MECP2 IN AUTISM SPECTRUM DISORDER (DSB.AD004.309)

Thematic area

Biomedical sciences

Project area

Structure responsible for the research project

Institute of neuroscience (IN)

Project manager

IRENE CORRADINI
Phone number: 0282245173
Email: irene.corradini@in.cnr.it

Abstract

Since the discovery of MECP2 mutations as the genetic cause of Rett syndrome (1), the understanding of MeCP2 function has largely evolved. Today it is recognized that either MeCP2 reductions or increases result in synapse dysfunctions and indeed MeCP2 loss- or gain-of-function leads to severe neurodevelopmental disorders, including autism spectrum disorder, Angelman's syndrome and learning disabilities (2,3). However, it is still unknown whether non-genetic factors impact MeCP2 expression.
By exploiting a genetic mouse model lacking IL-1R8, an IL-1² negative modulator, we unexpectedly found that hyperactivation of IL-1² signaling results in the up-regulation of MeCP2, leading to impairment in synaptic transmission and plasticity (4). Furthermore, we have preliminary results indicating that IL-6 produces instead reductions of MeCP2 expression. These data are very relevant, since i) optimal MeCP2 levels are required for a proper synapse function (5); ii) altered dosage of MeCP2 results in various disease phenotypes (6); iii) maternal immune activation (MIA), resulting in cytokine dysregulation, affects the risk and/or severity of a variety of neurodevelopmental disorders (7).
Aim of

Start date of activity

01/09/2020

Keywords

MeCP2, inflammation, autism

Last update: 19/04/2025